Derazantinib (ARQ 087)

Overview

Derazantinib (ARQ 087) is an oral, multi-kinase inhibitor designed to preferentially inhibit the FGFR (fibroblast growth factor receptor) family of kinases with demonstrated activity in FGFR2 genetic alterations, including fusions. ArQule entered into an exclusive license agreement with Basilea Pharmaceutica International Limited (Basilea, SIX: BSLN) to develop and commercialize derazantinib in the U.S., EU, Japan and rest of the world excluding the People’s Republic of China, Hong Kong, Macau and Taiwan, where Sinovant Sciences Ltd., a Roivant Sciences Ltd. subsidiary, has rights to develop and exclusively commercialize the drug.

Mechanism of Action

Fibroblast growth factors and their receptors tightly regulate key cellular behaviors, such as proliferation, cell differentiation, cell migration, cell survival and angiogenesis. In human cancers, FGFRs have been found to be dysregulated by multiple mechanisms, including aberrant expression, mutations, chromosomal rearrangements, and amplifications. FGFR dysregulation has been identified as a driver in a number of cancers, including iCCA (intrahepatic cholangiocarcinoma), cholangiocarcinoma, bladder, endometrial, breast, gastric, lung and ovarian cancers. Current scientific literature suggests FGFR alterations exist in anywhere from 5% to 40% of these cancers. Derazantinib is a potent FGFR inhibitor that shows strong anti-proliferative activity in cell lines harboring FGFR2 alterations. In clinical testing the molecule has demonstrated activity in cancerous tumors harboring FGFR2 fusions in iCCA and bladder cancers.

On-going Phase 3 Trial in iCCA

Intrahepatic cholangiocarcinoma (iCCA) (bile duct cancer) is a rare and difficult to treat cancer that occurs in the small, tube-like bile ducts within the liver that carry bile to the gallbladder. Although rare, iCCA is an aggressive form of cancer with limited treatments beyond surgical intervention and very poor response rates to chemotherapy. Current treatment is based on the patient’s stage of the cancer when diagnosed and is often limited to supportive care due to progression free survival averaging between 2-3 months.

Derazantinib is currently in a registrational trial as a second line treatment for FGFR2 fusion iCCA patients with the key objective of demonstrating efficacy via overall response rate, progression free survival, overall survival and duration of response, in addition to safety.